Cardiac AAV gene therapy: Translational lessons from intracoronary cardiomyocyte-targeted delivery

Cardiovascular gene therapy is entering a translationally distinct era in which the central challenge may no longer be whether myocardial gene transfer is biologically feasible, but rather how to optimize vector engineering, route of administration, tissue tropism, immunogenicity, and dose selection to achieve durable cardiac biologic activity with clinically acceptable systemic exposure. In our recently published first-in-human study in Nature Medicine, we tested AB-1002, an investigational cardiotropic adeno-associated vector (AAV)-mediated intracoronary gene therapy expressing constitutively active inhibitor-1 (I-1c), in patients with heart failure, providing mechanistic and translational insights into this evolving therapeutic paradigm.